TY - JOUR T1 - Structural basis for recognition of diverse antidepressants by the human serotonin transporter JF - bioRxiv DO - 10.1101/204859 SP - 204859 AU - Jonathan A. Coleman AU - Eric Gouaux Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/10/17/204859.abstract N2 - Selective serotonin reuptake inhibitors are clinically prescribed antidepressants that act by increasing the local concentration of neurotransmitter at synapses and in extracellular spaces via blockade of the serotonin transporter. Here we report x-ray structures of engineered thermostable variants of the human serotonin transporter bound to the antidepressants sertraline, fluvoxamine, and paroxetine. The drugs prevent serotonin binding by occupying the central substrate binding site and stabilizing the transporter in an outward-open conformation. These structures explain how residues within the central site orchestrate binding of chemically diverse inhibitors and mediate transporter-drug selectivity. ER -